Research on aspartate transcarbomylase (ATCase) is aimed at determining the mechanism of the allosteric transition whereby this regulatory enzyme is converted from a low-affinity or constrained state to a relaxed form having a high affinity for substrates. Conformational changes are being measured by hydrodynamic, chemical, spectroscopic, and calorimetric techniques to determine the linkage between alterations in quaternary structure to those in tertiary structure. Both inter- and intra-subunit hybrids comprising wild-type and mutant catalytic subunits along with wild-type regulatory subunits are being studied so as to understand how the active chains are constrained into a relatively inactive form in the oligomer. Similar hybrids containing chemically modified polypeptide chains are being used to study "communication" or "cross-talk" between catalytic subunits as ligands which bind to active chains promote a change in the inactive ones through the mediation of the regulatory subunits. Chromophores introduced as probes on the catalytic chains are being employed to determine the gross effects of the inhibitor and activator which bind to the regulatory chains. The strength of the inter-subunit bonding domains is being studied by many techniques so as to measure the effect of ligands on those "bonds". Our overall goal is to provide an understanding of allostery for this enzyme and also to evaluate general principles and develop techniques for investigating other oligomeric proteins.